rs1353258

chr5-14855550-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054027.6(ANKH):c.96+15802C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,904 control chromosomes in the GnomAD database, including 29,951 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29951 hom., cov: 31)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

Genes affected

ANKH (HGNC:15492): (ANKH inorganic pyrophosphate transport regulator) This gene encodes a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. Progressive ankylosis-mediated control of pyrophosphate levels has been suggested as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals. Mutations in this gene have been associated with autosomal dominant craniometaphyseal dysplasia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.96+15802C>A		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.96+15802C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.96+15802C>A		intron_variant		1	NM_054027.6	P1
ANKH	ENST00000513115.1	n.121+15802C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94537 AN: 151786 Hom.: 29879 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.575

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.623 AC: 94677 AN: 151904 Hom.: 29951 Cov.: 31 AF XY: 0.628 AC XY: 46641 AN XY: 74222

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.580

Alfa AF: 0.568 Hom.: 23362

Bravo AF: 0.626

Asia WGS AF: 0.773 AC: 2689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.1
Dann	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1353258; hg19: chr5-14855659;